Origin of new genes: evidence from experimental and computational analyses.

Long M, Deutsch M, Wang W, Betran E, Brunet FG, Zhang J.Department of Ecology and Evolution, The University of Chicago,

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Exon shuffling is an essential molecular mechanism for the formation of new genes. Many cases of exon shuffling have been reported in vertebrate genes. These discoveries revealed the importance of exon shuffling in the origin of new genes. However, only a few cases of exon shuffling were reported from plants and invertebrates, which gave rise to the assertion that the intron-mediated recombination mechanism originated very recently. We focused on the origin of new genes by exon shuffling and retroposition. We will first summarize our experimental work, which revealed four new genes in Drosophila, plants, and humans. These genes are 10(6) to 10(8) million years old. The recency of these genes allows us to directly examine the origin and evolution of genes in detail. These observations show firstly the importance of exon shuffling and retroposition in the rapid creation of new gene structures. They also show that the resultant chimerical structures appearing as mosaic proteins or as retroposed coding structures with novel regulatory systems, often confer novel functions. Furthermore, these newly created genes appear to have been governed by positive Darwinian selection throughout their history, with rapid changes of amino acid sequence and gene structure in very short periods of evolution. We further analyzed the distribution of intron phases in three non-vertebrate species, Drosophila melanogaster, Caenorhabditis elegans, and Arabidosis thaliana, as inferred from their genome sequences. As in the case of vertebrate genes, we found that intron phases in these species are unevenly distributed with an excess of phase zero introns and a significant excess of symmetric exons. Both findings are consistent with the requirements for the molecular process of exon shuffling. Thus, these non-vertebrate genomes may have also been strongly impacted by exon shuffling in general.

Humans and other Anthropoids share very similar chromosome structure and genomic sequence as seen in the 98.5% homology at the DNA level between us and Great Apes. However, anatomical and behavioral traits distinguish Homo sapiens from his closest relatives. I review here several recent studies that address the issue by using different approaches: large-scale sequence comparison (first release) between human and chimpanzee, characterization of recent segmental duplications in the human genome and analysis of exemplary gene families. As a major breakthrough in the field, the heretical concept of 'human-specific' genes has recently received some supporting data. In addition, specific chromosomal regions have been mapped that display all the features of 'gene nurseries' and could have played a major role in gene innovation and speciation during primate evolution. A model is proposed that integrates all known molecular mechanisms that can create new genes in the human lineage.